Abstract
The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses. By analogy with the rodent cardioviruses, SAFV may be a relevant new human pathogen. Thus far, SAFVs have sporadically been detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance remained unclear. Here we describe the first cultivated SAFV type 3 (SAFV-3) isolate, its growth characteristics, full-length sequence, and epidemiology. Unlike the previously isolated SAFV-1 and -2 viruses, SAFV-3 showed efficient growth in several cell lines with a clear cytopathic effect. The latter allowed us to conduct a large-scale serological survey by a virus-neutralization assay. This survey showed that infection by SAFV-3 occurs early in life (>75% positive at 24 months) and that the seroprevalence reaches >90% in older children and adults. Neutralizing antibodies were found in serum samples collected in several countries in Europe, Africa, and Asia. In conclusion, this study describes the first cultivated SAFV-3 isolate, its full-length sequence, and epidemiology. SAFV-3 is a highly common and widespread human virus causing infection in early childhood. This finding has important implications for understanding the impact of these ubiquitous viruses and their possible role in acute and/or chronic disease.
Highlights
Recent advances in molecular detection methods have led to the identification of many new viruses which are detected in symptomatic, but in individuals without any clinical manifestation
A new picornavirus was isolated from humans, named Saffold virus (SAFV)
SAFVs have been sporadically detected by molecular techniques in respiratory and fecal specimens, but the epidemiology and clinical significance have remained unclear
Summary
Recent advances in molecular detection methods (e.g. viral oligonucleotide microarrays and viral metagenomics approaches) have led to the identification of many new viruses which are detected in symptomatic, but in individuals without any clinical manifestation. The clinical outcome of a virus infection may depend upon the conditions under which the infection is acquired: For example, poliomyelitis was seldom observed under conditions of poor sanitation, congenital rubella syndrome is a consequence of postponed childhood infection and some types of cancer are late events in which certain viruses play a crucial role. It requires detailed insight in viral diversity, since it is well known that minor differences in the genetic make-up of viruses can cause major differences in their pathogenicity. The latter holds especially for RNA viruses such as the picornaviruses which due to their high mutation and recombination rates show remarkable genetic plasticity which may lead to serious pathology merely by accident [1]
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